LACK OF EVIDENCE FOR INDUCTION OF CYP2B1, CYP3A23, AND CYP1A2 GENE EXPRESSION BY <i>Panax ginseng</i> AND <i>Panax quinquefolius</i> EXTRACTS IN ADULT RATS AND PRIMARY CULTURES OF RAT HEPATOCYTES

Yu, Catherine; Chen, Jie; Teng, Xiao Wei; Tong, Vincent; Chang, Thomas K. H.

doi:10.1124/dmd.104.001917

Cited by 24 publications

(15 citation statements)

References 26 publications

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“…When Yu et al compared the effect of American ginseng and Asian ginseng extracts on gene expression of the hepatic P450 enzyme in adult rats and primary cultures or rat hepatocytes, there was no evidence of the induction of CYP2B1, CYP3A23, or CYP1A2 cultures of rat [47]. In another study ginseng had no effect on a number of CYP isoforms, including CYP3A4, CYP1A2, CYP2E1 and CYP2D6 [48, 49].…”

Section: Potential Ginseng-drug Interactionsmentioning

confidence: 99%

Metabolism of Ginseng and its Interactions with Drugs

Qi¹,

Wang²,

Du³

et al. 2011

CDM

101

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Ginseng is an herbal medicine used worldwide. It is reported to have a wide range of pharmacological activities because of a diversified group of steroidal saponins called ginsenosides. Compared to extensive pharmacological studies of ginseng, the pharmacokinetics, especially the metabolism of this herb, has received less attention. In this article we review the known pharmacokinetic data on ginseng. Understanding ginseng’s pharmacokinetics may reduce the potential for interactions in patients who use both ginseng and prescription medications. In addition, bioavailability after taking ginseng orally is low, and the metabolites of ginsenosides produced by gut microbiota may be biologically active. One ginseng metabolite, Compound K, and its potential for cancer chemoprevention is also discussed. An active ginseng metabolite may differ in distribution and clearance from its parent compound, and the parent compound and its metabolite may be bioactive by similar or different mechanisms. Thus, further investigation of ginseng metabolites is needed for predicting the therapeutic outcome with ginseng.

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Section: Potential Ginseng-drug Interactionsmentioning

confidence: 99%

Metabolism of Ginseng and its Interactions with Drugs

Qi¹,

Wang²,

Du³

et al. 2011

CDM

101

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“…Liu et al found that PPT and PPD, the deglycosylation products of naturally occurring ginsenosides, exhibited potent inhibition against CYP3A4 activity, and compound K and ginsenoside Rh2, which are more concentrated in fermented red ginseng than in red ginseng or fresh ginseng, also exhibited moderate inhibition of CYP2C9 and CYP3A4 activity . Moreover, many in vitro studies have supported the idea that the ginsenosides, including ginsenoside Rb1, Rb2, Rc and Rg1, in fresh ginseng do not affect CYP enzyme activity but that metabolites of these inhibit CYP1A2, CYP2C9 and CYP3A4 . However, in this study, oral administration of fermented red ginseng inhibited CYP1A2 enzyme activity, but this effect is unlikely to cause significant interactions.…”

Section: Discussionmentioning

confidence: 99%

“…In a previous study, Yu et al compared the effects of American ginseng ( Panax quinquefolius ) and Asian ginseng ( Panax ginseng ) extracts on gene expression of the hepatic P450 enzyme in adult rats and primary cultures or rat hepatocytes . They found no evidence of the induction of CYP2B1, CYP3A23 or CYP1A2 in rat cultures.…”

Section: Discussionmentioning

confidence: 99%

Effect of fermented red ginseng on cytochrome P450 and P‐glycoprotein activity in healthy subjects, as evaluated using the cocktail approach

Kim

Jeon

et al. 2016

Brit J Clinical Pharma

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AimsWe assessed the drug interaction profile of fermented red ginseng with respect to the activity of major cytochrome (CYP) P450 enzymes and of a drug transporter protein, P‐glycoprotein (P‐gp), in healthy volunteers.MethodsThis study was an open‐label crossover study. The CYP probe cocktail drugs caffeine, losartan, dextromethorphan, omeprazole, midazolam and fexofenadine were administered before and after 2 weeks of fermented red ginseng administration. Plasma samples were collected, and tolerability was assessed. Pharmacokinetic parameters were calculated, and the 90% confidence intervals (CIs) of the geometric mean ratios of the parameters were determined from logarithmically transformed data. Values were compared between before and after fermented red ginseng administration using analysis of variance (anova).ResultsFifteen healthy male subjects were evaluated, none of whom were genetically defined as a poor CYP2C9, CYP2C19 or CYP2D6 metabolizer based on genotyping. Before and after fermented red ginseng administration, the geometric least‐square mean metabolic ratio (90% CI) was 0.901 (0.830–0.979) for caffeine (CYP1A2) to paraxanthine, 0.774 (0.720–0.831) for losartan (CYP2C9) to EXP3174, 1.052 (0.925–1.197) for omeprazole (CYP2C19) to 5‐hydroxyomeprazole, 1.150 (0.860–1.538) for dextromethorphan (CYP2D6) to dextrorphan, and 0.816 (0.673–0.990) for midazolam (CYP3A4) to 1‐hydroxymidazolam. The geometric mean ratio of the area under the curve of the last sampling time (AUClast) for fexofenadine (P‐gp) was 1.322 (1.112–1.571).ConclusionNo significantly different drug interactions were observed between fermented red ginseng and the CYP probe substrates following the two‐week administration of concentrated fermented red ginseng. However, the inhibition of P‐gp was significantly different between fermented red ginseng and the CYP probe substrates. The use of fermented red ginseng requires close attention due to the potential for increased systemic exposure when it is used in combination with P‐gp substrate drugs.

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“…Our results imply a possible clinical interaction between the two drugs, but should be eventually confirmed in an in vivo study. In a recent study performed after oral administration of G115 extract to rats, it was shown that it does not induce CYP2B1,CYP3A23 or CYP1A2 (P450 isoenzymes) gene expression (Yu et al, 2005). Interaction studies are of major importance since herbal remedies are sold without prescription and often used without the knowledge of the patient's physician.…”

Section: Discussionmentioning

confidence: 98%